CCTN September 6 th, 2011

Recent Scientific Publications from the Clinical Trials Network David Liu, M.D. (CTN-0029) Harold Perl, Ph.D. (CTN-0015) Paul Wakim, Ph.D. (Secondary analysis of 8 CTN trials) Betty Tai, Ph.D. Director

Divergence by ADHD Subtype in Smoking Cessation Response to OROS-Methylphenidate Lirio S. Covey et al. Nicotine & Tobacco Research Available online June 7, 2011

CTN-0029 Clinical Trial Double-blind, randomized clinical trial for adult smokers with ADHD Double-blind, randomized clinical trial for adult smokers with ADHD n = 255; 6 sites n = 255; 6 sites Osmotic-release methylphenidate (OROS-MPH) vs. placebo for 11 weeks Osmotic-release methylphenidate (OROS-MPH) vs. placebo for 11 weeks Nicotine patches and weekly smoking cessation counseling Nicotine patches and weekly smoking cessation counseling Primary outcome: No improvement in prolonged abstinence rate, OROS-MPH vs. placebo Primary outcome: No improvement in prolonged abstinence rate, OROS-MPH vs. placebo CTN-0029 Covey et al., Nicotine & Tobacco Research 2011

Covey et al. Logistic Regression Model Dependent variable: Prolonged abstinence Dependent variable: Prolonged abstinence Independent variables: Independent variables: ADHD subtype (inattentive vs. hyperactive/impulsive or combined) ADHD subtype (inattentive vs. hyperactive/impulsive or combined) Total ADHD symptoms at baseline Total ADHD symptoms at baseline Nicotine dependence level (Fagerström) Nicotine dependence level (Fagerström) Smoking history Smoking history Psychiatric history Psychiatric history Demographic characteristics Demographic characteristics Randomized treatment (OROS-MPH vs. placebo) Randomized treatment (OROS-MPH vs. placebo) CTN-0029 Covey et al., Nicotine & Tobacco Research 2011

Results Prolonged abstinence rates by nicotine dependence level (FTND), ADHD subtype, and randomized treatment: CTN-0029 Covey et al., Nicotine & Tobacco Research way interaction: χ 2 (1) = 8.22, p <.01 Prolonged Abstinence %

Implications Assessment of ADHD subtype and of nicotine dependence level could be part of a personalized treatment approach for smokers with ADHD Assessment of ADHD subtype and of nicotine dependence level could be part of a personalized treatment approach for smokers with ADHD Highly nicotine dependent smokers with ADHD, hyperactive-impulsive or combined subtype, may benefit from OROS-MPH treatment Highly nicotine dependent smokers with ADHD, hyperactive-impulsive or combined subtype, may benefit from OROS-MPH treatment OROS-MPH may not be a treatment of choice for highly nicotine dependent smokers with ADHD, inattentive subtype OROS-MPH may not be a treatment of choice for highly nicotine dependent smokers with ADHD, inattentive subtype CTN-0029 Covey et al., Nicotine & Tobacco Research 2011

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Recruitment Affects Sample Clinical trials recruit directly from treatment programs or through general advertising Recruitment method can impact sample composition – and generalizability – of a trial Little study of this in SUD trials Particularly few data on relationship between recruitment and outcome Winhusen, T., et al., Drug Alcohol Depend. (2011) doi: /j.drugalcdep

Newspaper Ads vs. Clinic Recruits Study compares participants at 1 site – N = 70 recruited from newspaper advertisements – N = 36 recruited directly from clinic patients

Newspaper Ads vs. Clinic Recruits Study compares participants at 1 site – N = 70 recruited from newspaper advertisements – N = 36 recruited directly from clinic patients Examines relationship of recruitment with – sample characteristics – treatment outcomes Winhusen, T., et al., Drug Alcohol Depend. (2011) doi: /j.drugalcdep

Recruiting Method & Treatment Effectiveness Ad recruits had higher levels of drug use and PTSD at baseline than clinic recruits Seeking Safety was more effective for ad recruits in reducing PTSD than for clinic recruits (although SS effective for all) Seeking Safety was more effective for clinic recruits in reducing past week drug use at follow-up Winhusen, T., et al., Drug Alcohol Depend. (2011) doi: /j.drugalcdep

Implications for Study Design Recruitment method can affect – Sample characteristics – Treatment effectiveness – Trial generalizability Important to take recruiting methods into account during study design phase Winhusen, T., et al., Drug Alcohol Depend. (2011) doi: /j.drugalcdep

Volume 37, Number 5 (September 2011)

Objectives 1)To examine the prevalence of alcohol use disorders among primary stimulant-misusing treatment-seekers 2)To examine the impact of alcohol use disorder comorbidity on their pre-treatment psychosocial functioning Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)

Results: Prevalence of alcohol use disorder Total from 8 trials: 4,396 participants  Stimulant misusers: 1,133 (26%)  With data on alcohol use: 993 (88%)  With AUD comorbidity: 449 (45%) Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)

Results: Primary Cocaine Misusers 48% had AUD comorbidity Those with AUD were more likely to: 1)show elevated ASI composite scores 2)perceive greater importance of drug treatment 3)endorse psychiatric symptoms and perceived need for their (psychiatric) treatment Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)

Results: Primary Amphetamine Misusers 35% had AUD comorbidity Those with AUD were more likely to endorse specific psychiatric symptoms (dyscontrol of violence, suicidal ideation and attempted suicide) Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)

Conclusion AUD comorbidity is a fairly common diagnostic feature of primary stimulant misusers AUD has a pervasive influence on the pre- treatment psychosocial functioning of cocaine misusers Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)

Conclusion In addiction treatment research: Include a comprehensive diagnostic assessment Stratify by diagnostic variables In clinical practice: Comprehensively diagnose substance use disorders in treatment intake and treat accordingly Hartzler, B., et al., AM J Drug and Alcohol Abuse 37: (2011)